Comparing Whole Brain Radiotherapy Using a Technique That Avoids the Hippocampus to Stereotactic Radiosurgery in Patients With Cancer That Has Spread to the Brain and Come Back in Other Areas of the Brain After Earlier Stereotactic Radiosurgery

PRIMARY OBJECTIVE: I. To determine if hippocampal-avoidant plus whole brain radiotherapy (HA-WBRT) in patients with distant brain failure with brain metastasis velocity \>= 4 new brain metastases/year prolongs time to neurologic death as compared to stereotactic radiosurgery (SRS). SECONDARY OBJECTIVES: I. To determine if HA-WBRT in patients with distant brain failure with brain metastasis velocity \>= 4 new brain metastases/year prolongs overall survival as compared to SRS. II. To evaluate if HA-WBRT in patients with distant brain failure with brain metastasis velocity \>= 4 new brain metastases/year prolongs intracranial progression-free survival as compared to SRS. III. To evaluate if HA-WBRT in patients with distant brain failure with brain metastasis velocity \>= 4 new brain metastases/year improves brain metastasis velocity at subsequent relapse as compared to SRS. IV. To assess perceived difficulties in cognitive abilities, symptom burden and health status after HA-WBRT, as compared to SRS, in patients with distant brain failure with brain metastasis velocity \>= 4 new brain metastases/year. V. To compare neurocognitive function outcomes following HA-WBRT, as compared to SRS, in patients with distant brain failure with brain metastasis velocity \>= 4 new brain metastases/year. VI. To tabulate and descriptively compare the adverse events associated with the interventions. VII. To tabulate and descriptively compare the number of salvage procedures used to manage recurrent intracranial disease following the interventions. EXPLORATORY OBJECTIVES: I. To collect serum, plasma, and whole blood for translational research analyses. II. To collect baseline and all follow-up magnetic resonance (MR) imaging for hippocampal volume, memory center substructures, axial T2 volumes, and quantitative texture analysis. III. To collect baseline and follow-up MR imaging to extract whole brain volume, white matter volume and volume of metastatic disease to correlate with cognitive change at 4 months. IV. To evaluate dose-volume histogram parameters to correlate with radiation toxicity. V. To assess in patients receiving immunotherapy or targeted therapy, if HA-WBRT in patients with distant brain failure with brain metastasis velocity \>= 4 new brain metastases/year at time improves brain metastasis velocity and/or overall survival at subsequent relapse as compared to SRS. VI. To compare the estimated cost of brain-related therapies and quality-adjusted life years in patients who receive HA-WBRT, as compared to SRS, in patients with distant brain failure with metastasis velocity \>= 4 new brain metastases/year. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients undergo HA-WBRT daily (5 times weekly) for 2 weeks for a total of 10 fractions in the absence of disease progression or unacceptable toxicity. Prior to HA-WBRT or no later than the 4th treatment, patients also receive memantine orally (PO) once daily (QD) or twice daily (BID) for 24 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) and magnetic resonance imaging (MRI) and may undergo blood sample collection throughout the trial. ARM II: Patients undergo single fraction SRS or fractionated SRS (fSRS) on study. Patients also undergo CT and MRI and may undergo blood sample collection throughout the trial. Patients are followed up at 2, 4, 6, 9, and 12 months from the start of SRS/fSFS or HA-WBRT and then every 6 months after month 12 and within 21 days after patient death.