You can safely delete the entire contents of the SoftwareDistribution folder, but it's quite likely that any Windows Updates you've chosen to hide will return and nee re-hiding. That's why I just delete the Downloads folder.
Just use Disk Cleanup to remove the Windows Update cache.
I tend to do it manually on my base images at work to allow deployed PCs to force a full check on the first check. If you do do it manually stop the Windows Update service first before deleting the contents of SoftwareDistribution.
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