Mayo Clinic-led and Alliance/NRG-style randomized evidence converged on a key postoperative radiotherapy question: how to fraction stereotactic radiosurgery to reduce local recurrence. In a randomized phase III Alliance trial, delivering postoperative radiosurgery in three to five sessions instead of a single session reduced recurrence at the surgical site and extended median survival by about nine months for patients with large brain metastases. A separate Phase III NRG Oncology trial reported that stereotactic radiosurgery nearly doubled median survival in small cell lung cancer patients with brain metastases without improving neurocognitive outcomes versus hippocampal-avoidant whole-brain radiotherapy. Together, the studies underscore that fractionation and patient selection matter for balancing tumor control with long-term functional risk. For clinicians and drug developers tied to neuro-oncology endpoints, these results provide sharper benchmarks for trial design—especially for studies testing systemic therapies alongside evolving local-control radiotherapy standards.