Until recently, brain metastases were considered an end-stage progression of cancer best managed palliatively. However, more aggressive therapeutic approaches for brain metastases are increasingly warranted for several reasons including (1) their incidence is increasing in tandem with improving cancer survival, (2) the central nervous system (CNS) is increasingly an isolated site of refractory and life-limiting disease, and (3) outcomes are improving, making optimized long-term control necessary in an increasing proportion of patients. In issuing its landmark 2020 guidance on the inclusion of patients with brain metastasis in clinical trials, the US Food and Drug Administration (FDA) cited an urgent mandate to direct “…attention…to address this unmet clinical need…”1 and effectively challenged the oncology community to stop excluding and to extend its focus to this population.