Lizza Hendriks, MD, PhD, Maastricht University, Maastricht, Netherlands, discusses the systemic treatment of patients with non-small cell lung cancer (NSCLC) and brain metastases who are non-oncogene addicted. Dr Hendriks outlines the challenges associated with asymptomatic brain metastases in NSCLC and highlights the importance of screening for brain metastases. Dr Hendriks then discussess recommendations for the treatment of patients with NSCLC and brain metastases, outlining the limitations of recommendations which are primarily based on small trials or subgroup analyses of larger trials, and highlights trials where platinum-based chemotherapy have demonstrated a similar response rate in the brain as elsewhere. Dr Hendriks also discusses the use of immune checkpoint inhibitors for patients with NSCLC and brain metastases, highlighting data from the Phase III KEYNOTE-189 (NCT02578680) trial, and outlines data on pembrolizumab monotherapy. This video was recorded at the virtual European Lung Cancer Congress (ELCC) 2021.